Adenovirus is a double-stranded DNA virus with a genome size of about 36 kilobases (kb), which has been widely used for gene transfer applications due to its ability to achieve highly efficient gene transfer in a variety of target tissues and large transgene capacity. Conventionally, E1 genes of adenovirus are deleted and replaced with a transgene cassette consisting of the promoter of choice, cDNA sequence of the gene of interest and a poly A signal, resulting in a replication defective recombinant virus.
Adenoviruses have a characteristic morphology with an icosahedral capsid consisting of three major proteins, hexon (II), penton base (III) and a knobbed fibre (IV), along with a number of other minor proteins, VI, VIII, IX, IIIa and IVa2 [W. C. Russell, J. Gen Virol., 81:2573-2604 (November 2000)]. The virus genome is a linear, double-stranded DNA having inverted terminal repeats (ITRs), with a terminal protein attached covalently to the 5′ termini. The virus DNA is intimately associated with the highly basic protein VII and a small peptide termed mu. Another protein, V, is packaged with this DNA-protein complex and provides a structural link to the capsid via protein VI. The virus also contains a virus-encoded protease, which is necessary for processing of some of the structural proteins to produce mature infectious virus.
Recombinant adenoviruses have been described for delivery of molecules to host cells to induce an immune response. See, U.S. Pat. No. 6,083,716, which provides adenoviral vectors derived from the two chimpanzee adenoviruses, C1 and C68 (also termed Pan 9) and International Patent Publication No. WO 02/33645 [Pan 5, Pan6, Pan7-derived vectors].
What is needed in the vaccine field is method of immunizing that will induce a strong immune response with minimal responses to the vaccine carrier.